Chondroitin sulfate is an important component of the extracellular matrix of animals. Chondroitin 6-sulfate (C6S), the form that is sulfated at position 6 of its N-acetylgalactosamine residues, has been implicated in several key roles in human biology, including development (Toledo et al. Am. J. Med. Gen. 1978, 2:385-395; Mourao et al, Biochem. Biophys. Res. Commun. 1981, 98:388-396; Habuchi et al. J. Biol. Chem. 1986, 261:1031-1040), cancer (Adany et al. J. Biol. Chem. 1990, 265:11389-11396), and atherosclerosis (Williams, K. J. and Tabas, I. Arterioscl. Thromb. Vasc. Biol. 1995, 15:551-561). The abundance of C6S is under genetic (Edwards, I. J. and Wagner, W. D. J. Biol. Chem. 1988, 263:9612-9620) and stimulatory (Schonherr et al. J. Biol. Chem. 1991, 266:17640-17647) control. Fukata et al. recently cloned the chick cDNA encoding C6ST, the essential enzyme in C6S synthesis (J. Biol. Chem. 1995, 270:18575-18580).
A human genomic DNA encoding C6ST has now been cloned and sequenced.
An object of the present invention is to provide a gene encoding human chondroitin 6-sulfotransferase.
Another object of the present invention is to provide vectors comprising genes encoding human chondroitin 6-sulfotransferase and host cells containing these vectors.
Yet another object of the present invention is to provide polypeptides encoded by human chondroitin 6-sulfotransferase.
Yet another object of the present invention is to provide nonhuman transgenic animals capable of encoding a gene of the present invention.
Yet another object of the present invention is to provide methods of identifying activators and inhibitors of expression, activities and biologic effects of human chondroitin 6-sulfotransferase.
Still another object of the present invention is to provide methods of identifying mutations in the genes encoding human chondroitin 6-sulfotransferase.